Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17222 | 51889;51890;51891 | chr2:178609759;178609758;178609757 | chr2:179474486;179474485;179474484 |
| N2AB | 15581 | 46966;46967;46968 | chr2:178609759;178609758;178609757 | chr2:179474486;179474485;179474484 |
| N2A | 14654 | 44185;44186;44187 | chr2:178609759;178609758;178609757 | chr2:179474486;179474485;179474484 |
| N2B | 8157 | 24694;24695;24696 | chr2:178609759;178609758;178609757 | chr2:179474486;179474485;179474484 |
| Novex-1 | 8282 | 25069;25070;25071 | chr2:178609759;178609758;178609757 | chr2:179474486;179474485;179474484 |
| Novex-2 | 8349 | 25270;25271;25272 | chr2:178609759;178609758;178609757 | chr2:179474486;179474485;179474484 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | None | None | 0.942 | D | 0.802 | 0.747 | 0.826887190631 | gnomAD-4.0.0 | 3.18682E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.76634E-05 | 0 | 0 | 0 | 0 |
| V/G | rs1014056487  |
-3.597 | 0.698 | D | 0.813 | 0.719 | 0.777313054034 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87853E-04 | 0 | 0 |
| V/G | rs1014056487 |
-3.597 | 0.698 | D | 0.813 | 0.719 | 0.777313054034 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| V/G | rs1014056487 |
-3.597 | 0.698 | D | 0.813 | 0.719 | 0.777313054034 | gnomAD-4.0.0 | 2.56573E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.13853E-05 | 0 | 0 | 0 | 0 |
| V/M | None | None | 0.99 | D | 0.646 | 0.631 | 0.729886986044 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9361 | likely_pathogenic | 0.892 | pathogenic | -2.564 | Highly Destabilizing | 0.006 | N | 0.332 | neutral | D | 0.548364838 | None | None | N |
| V/C | 0.9766 | likely_pathogenic | 0.9733 | pathogenic | -1.982 | Destabilizing | 0.994 | D | 0.742 | deleterious | None | None | None | None | N |
| V/D | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -3.504 | Highly Destabilizing | 0.978 | D | 0.867 | deleterious | None | None | None | None | N |
| V/E | 0.9979 | likely_pathogenic | 0.997 | pathogenic | -3.204 | Highly Destabilizing | 0.942 | D | 0.802 | deleterious | D | 0.63969891 | None | None | N |
| V/F | 0.9856 | likely_pathogenic | 0.98 | pathogenic | -1.418 | Destabilizing | 0.978 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/G | 0.9613 | likely_pathogenic | 0.9472 | pathogenic | -3.131 | Highly Destabilizing | 0.698 | D | 0.813 | deleterious | D | 0.63969891 | None | None | N |
| V/H | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -2.942 | Highly Destabilizing | 0.998 | D | 0.867 | deleterious | None | None | None | None | N |
| V/I | 0.2253 | likely_benign | 0.2061 | benign | -0.907 | Destabilizing | 0.717 | D | 0.525 | neutral | None | None | None | None | N |
| V/K | 0.9986 | likely_pathogenic | 0.9982 | pathogenic | -2.093 | Highly Destabilizing | 0.956 | D | 0.821 | deleterious | None | None | None | None | N |
| V/L | 0.9181 | likely_pathogenic | 0.8992 | pathogenic | -0.907 | Destabilizing | 0.489 | N | 0.613 | neutral | N | 0.519292217 | None | None | N |
| V/M | 0.969 | likely_pathogenic | 0.9595 | pathogenic | -1.181 | Destabilizing | 0.99 | D | 0.646 | neutral | D | 0.529526568 | None | None | N |
| V/N | 0.9978 | likely_pathogenic | 0.9971 | pathogenic | -2.717 | Highly Destabilizing | 0.978 | D | 0.883 | deleterious | None | None | None | None | N |
| V/P | 0.9976 | likely_pathogenic | 0.997 | pathogenic | -1.443 | Destabilizing | 0.978 | D | 0.844 | deleterious | None | None | None | None | N |
| V/Q | 0.9979 | likely_pathogenic | 0.9972 | pathogenic | -2.394 | Highly Destabilizing | 0.978 | D | 0.868 | deleterious | None | None | None | None | N |
| V/R | 0.9959 | likely_pathogenic | 0.9949 | pathogenic | -2.078 | Highly Destabilizing | 0.956 | D | 0.885 | deleterious | None | None | None | None | N |
| V/S | 0.9864 | likely_pathogenic | 0.9797 | pathogenic | -3.203 | Highly Destabilizing | 0.754 | D | 0.783 | deleterious | None | None | None | None | N |
| V/T | 0.9685 | likely_pathogenic | 0.9591 | pathogenic | -2.762 | Highly Destabilizing | 0.86 | D | 0.601 | neutral | None | None | None | None | N |
| V/W | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.996 | Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| V/Y | 0.9985 | likely_pathogenic | 0.998 | pathogenic | -1.729 | Destabilizing | 0.993 | D | 0.743 | deleterious | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.